, Volume 172, Issue 4, pp 375-383

AR-R 17779 improves social recognition in rats by activation of nicotinic α7 receptors

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Abstract

Rationale

Nicotine and agonists at α4β2 and α7 nicotinic acetylcholine receptors (nAChRs) improve learning and memory. The α7-nAChR subtype is of special interest, since it appears to play no role in the abuse liability of nicotine.

Objectives and methods

To further investigate the role of the α7-nAChR in learning and memory, the effects of the specific α7-nAChR agonist AR-R17779 on cognition were measured in the rat social recognition test (SRT) and the effect of the α7-nAChR antagonist methyllycaconitine (MLA) was studied. The SRT and a scopolamine-induced deficit version were validated with the acetylcholinesterase inhibitor metrifonate. Social memory was measured by the ability of an adult rat to recognize a juvenile rat after a delay. The difference in social interaction time (SIT) was measured between two encounters. The difference in SIT is expressed as percent reduction in social interaction time (%RSIT).

Results

Metrifonate (10 and 30 mg/kg PO) increased %RSIT in a behaviorally specific manner, employing a 24-h interval and reversed the scopolamine-induced deficit at a retention time of 15 min. Likewise, AR-R17779 increased %RSIT in unimpaired animals (1, 3, 10 and 30 mg/kg SC) employing a 24-h retention interval, and reversed the scopolamine-induced deficit (0.3 and 1 mg/kg SC) after a 15-min retention interval. The effects of AR-R17779 (1 mg/kg SC) in unimpaired animals were reversed by MLA (10 µg ICV), which induced a decrease of %RSI at a 15-min retention interval when given alone.

Conclusions

AR-R17779 increased social recognition memory by activation of α7-nAChRs, suggesting that α7-nAChR agonists possess cognitive-enhancing properties.